Horizon Therapeutics announced that the primary endpoint was met for the second population in its Phase 2 clinical trial evaluating dazodalibep for the treatment of Sjögren’s syndrome.
The phase 2 trial evaluated two patient populations and positive results in the first patient population were announced in September 2022.
Dazodalibep is the only medicine in development to achieve the primary endpoint in both patient populations in a phase 2 trial.
Today, the Company announced that the second population achieved the primary endpoint. This patient population includes those with moderate-to-severe symptomatology including dryness, pain and fatigue despite lacking additional organ involvement and is defined as patients with a European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Patient Reported Index (ESSPRI) score of ≥ 5, indicative of significant symptomatic burden, and a score of <5 on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), which measures organ involvement.
At Day 169, dazodalibep-treated patients achieved a 1.8-point reduction in their ESSPRI scores compared to placebo-treated patients who achieved a 0.53-point reduction, resulting in a least squares mean difference of 1.27 (p=0.0002).
The ESSPRI is a composite endpoint that measures dryness, pain and fatigue severity.
The previously announced positive results were in patients with moderate-to-severe systemic disease: systemic clinical manifestations in one or more organ systems in addition to the traditional Sjogren’s manifestations, and an ESSDAI of ≥ 5.
“There are currently no disease-modifying FDA approved treatments for Sjögren’s and the population in this trial represents a large subset of patients who have a clear unmet clinical need,” said Frederick B. Vivino, MD, MS, former director of the Penn Sjögren's Center and chief, division of rheumatology at Penn Presbyterian Medical Center, University of Pennsylvania Perelman School of Medicine. “Participants in this study had been excluded from other recent trials, despite their substantial disease burden. The positive results from the Phase 2 trial are very promising in addressing many debilitating symptoms of people living with Sjogren’s.”
In addition to the primary endpoint, statistical significance was achieved in certain secondary quality of life measures, including fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).
Dazodalibep was well tolerated with the most common adverse events through Day 169 being COVID-19 infection, nasopharyngitis and anemia.
“It is remarkable to see how these data demonstrated a significant separation in symptom intensity in patients treated with dazodalibep compared to placebo and this reinforces the potential of dazodalibep’s mechanism of action for patients suffering with the disease,” said Elizabeth H.Z. Thompson, PhD, executive vice president, research and development, Horizon. “Following these positive data, we look forward to working with regulators to continue developing dazodalibep as a potential treatment to positively impact the severe symptomatology of people living with this disease and improve their quality of life.”
These data follow positive Phase 2 trial results announced in September in a separate study population. That portion of the study met its primary endpoint in patients with moderate-to-high systemic disease activity as defined by an ESSDAI score of ≥ 5.
At Day 169, patients treated with dazodalibep achieved a 6.3-point reduction in their ESSDAI score and patients treated with placebo achieved a 4.1-point reduction, resulting in a statistically significant least squares mean difference of 2.2 points (p=0.017).
Phase 2 Sjögren’s syndrome trial details
The Phase 2 study enrolled two Sjögren’s syndrome populations: the first included a total of 74 participants with moderate-to-high systemic disease activity defined by an ESSDAI score of ≥ 5 and the second included 109 participants with moderate-to-severe subjective symptoms defined by an ESSPRI score of ≥ 5 and residual stimulated salivary flow but with mild systemic disease activity defined by an ESSDAI score of < 5.
This study includes three periods: screening (4 weeks), treatment period (40 weeks), and follow-up period (12 weeks). In the treatment period, participants from each population were randomized at a 1:1 ratio to receive either intravenous (IV) doses of dazodalibep or placebo for 24 weeks (Stage 1).
After completion of Stage 1, participants who were randomized to the dazodalibep arm in Stage 1 received placebo and participants randomized to placebo in Stage 1 received dazodalibep for the remaining 16 weeks of the treatment period (Stage 2).
Participants who discontinued dazodalibep were not eligible for treatment during Stage 2.
All study participants were followed for at least 12 weeks after their last dose of study drug administration. Full trial data will be presented at medical meetings and published in scientific journals once available.